Pending further regulatory and institutional approvals, study could begin by end of 2016.

The first clinical trial using the genome-editing technology known as CRISPR is well on its way to reality. The National Institutes of Health DNA Advisory Committee gave its blessing in June for a study targeting melanoma, multiple myeloma, and sarcoma.

The study, proposed by researchers at the University of Pennsylvania and funded by the Parker Institute for Cancer Immunotherapy, still needs approval from the institutions that will conduct the trial, as well as from the Food and Drug Administration.

The first step in the study is to use a deactivated virus to insert a gene that makes a receptor for antigen NY-ESO-1, a protein found on cancer cells but not on most healthy cells. Adding the receptor to the T cells should make them more effective at recognizing the cancer cells as foreign and destroying them. A small study in patients with multiple myeloma using this approach found that targeting this molecule shrank tumor cells in nearly all patients tested. The problem is that the infused T cells became “exhausted,” and died or stopped functioning.

Using CRISPR to delete two genes should avoid this problem. One gene makes the PD-1 protein, which sits on the surface of many cells. Cancer cells that make their own PD-1 can “hide” from T cells and continue proliferating. Eliminating the gene should make the T-cell more effective against the cancer.

A second gene targeted for removal manufactures endogenous TCR, which identifies T cells as immune cells, marking them for destruction by the cancer cells. Removing this protein should enable the cells to better “hide” from cancer cells. Animal studies reveal that T cells function more effectively against certain cancer cells when this protein is missing.

The modified T cells will then be infused back into the patient with the hope that they will target and destroy cancer cells.

The Phase 1 study will be small, with just 15 patients, and is designed to test the safety of the therapy. If approved, it will be conducted at MD Anderson Cancer Center in Houston, the University of California in San Francisco, and the University of Pennsylvania in Philadelphia, and should begin at the end of the year.